1: The ?Mucus Slurper?[unreadable] [unreadable] In patients intubated with endotracheal tubes (ETT), suctioning is routinely performed to remove mucus from within the ETT, and the trachea. The Mucus Slurper is a novel ETT, with built-in suction ports arranged radially at its tip. In sheep mechanically ventilated for 72 hours, we evaluated safety and efficacy of the Mucus Slurper, compared to conventional tracheal suction, to prevent accumulation of secretions within the lumen of the ETT and trachea.[unreadable] [unreadable] 2: Tracheal mucus transport and the role of the ventilator in Ventilator Associated Pneumonia (VAP) [unreadable] [unreadable] Critically ill patients are usually positioned in the semi-recumbent position with the head of the bed elevated at an angle of 30-45 degrees, to prevent gastro-esophageal reflux, and pulmonary aspiration. [unreadable] [unreadable] We investigated the effects on tracheal mucus clearance after tracheal intubation in spontaneously breathing (without ventilator), or mechanically ventilated sheep, positioned with the trachea oriented above, or below horizontal. Our goal was also to determine whether impaired tracheal mucus clearance, combined with tracheal orientation above horizontal (as it is in semi-recumbent position in the human) was associated with increased risk for bacterial colonization of the lungs, and onset of pneumonia.[unreadable] [unreadable] Tracheal mucus velocity was measured via radiographic tracking of radiopaque tantalum disks and tantalum powder insufflated into the trachea.[unreadable] [unreadable] We found that after tracheal intubation, with the trachea elevated above horizontal, tracheal mucus clearance becomes highly abnormal, with mucus moving backward towards the lungs, followed by bacterial colonization of the lungs.[unreadable] [unreadable] 3: The ?Leak proof ETT cuff?[unreadable] [unreadable] Commercially available high-volume low-pressure cuffs (HVLP) were introduced to prevent pressure-related tracheal injury. In so doing, the cuff diameter was designed larger than the lumen of the trachea. Hence, with the tracheal cuff inflated within the trachea, folds always form. Leakage of colonized subglottic secretions along the folds can lead to colonization of the lower airways, and ventilator associated pneumonia (VAP). [unreadable] [unreadable] We manufactured a prototype ETT cuff by draping around the standard HVLP cuff a second, highly elastic cuff made of low-protein natural latex rubber, with a wall thickness of 40-50 microns. We introduced a small amount of aqueous lubricant into the space between the two cuffs to homogeneously distribute the distending pressure. [unreadable] [unreadable] Our studies until now have been confined to in vitro studies; in vivo testing and evaluation is to follow.[unreadable] [unreadable] 4: Prevention of VAP in mechanically ventilated pigs[unreadable] [unreadable] Based on previous animal studies in sheep sedated, intubated and mechanically ventilated, we have shown that when the head/neck are elevated 30-45 degrees above horizontal (as in the human in the semi-recumbent position), there was uniform, widespread tracheobronchial and lung bacterial colonization, starting within 24 h; followed by impaired gas exchange, and acute respiratory failure.[unreadable] [unreadable] When intubated sheep, on mechanical ventilation, were positioned so that the trachea and the tracheal tube were maintained horizontal, or with a slight incline downwards, and then mechanically ventilated for 72 h, there was no tracheal, bronchial, or lung parenchymal bacterial colonization. [unreadable] [unreadable] However, the transfer of pathophysiologic findings of pulmonary research in sheep, to human pathology, is difficult due to the different anatomical and physiologic conditions in ruminants and omnivores (such as the total amount of saliva produced per day, length of the trachea, oropharyngeal-rumen flora, etc.). [unreadable] [unreadable] We hence also studied mechanically ventilated omnivores (pigs), under general anesthesia and enteral feeding for 72-168 hours.[unreadable] [unreadable] This study showed that our findings in sheep, also apply to pigs.[unreadable] [unreadable] 5: Collaboration with medical research centers:[unreadable] [unreadable] Supported, by our laboratory finding to prevent VAP in 2 different animal models, we are now collaborating with 3 medical research centers (1. Massachusetts General Hospital - Drs. Zapol, Bigatello, Berra; 2. The University of Milan, Italy - Dr. Pesenti; 3. NIH Clinical Intensive Care Unit - Dr. Masur). We wish to start a multricenter trial on whether our approach to prevent VAP is feasible, safe, and effective in the critically ill human patient.